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A number of acceptable methods exist for analyzing TOC. This chapter does not limit or
prevent alternative technologies from being used, but provides guidance on how to qualify
these analytical technologies for use as well as guidance on how to interpret instrument
results for use as a limit test. The Standard Solution is a theoretically easy-to-oxidize solution
that gives an instrument response at the attribute limit. The analytical technology is qualified
by challenging the capability of the instrument using a theoretically difficult to oxidize solution
in the system suitability portion of the method.
Analytical technologies utilized to measure TOC share the objective of completely oxidizing
the organic molecules in an aliquot of sample water to carbon dioxide (CO2), measuring the
resultant CO2 levels, and expressing this response as carbon concentration. All technologies
must discriminate between the inorganic carbon, which may be present in the water from
sources such as dissolved CO2 and bicarbonate, and the CO2 generated from the oxidation
of organic molecules in the sample.
Two general approaches are used to measure TOC. One approach determines TOC by
subtracting the measured inorganic carbon (IC) from the measured total carbon (TC), which
is the sum of organic carbon and inorganic carbon:
TOC = TC – IC.
The other approach first purges the IC from the sample before any carbon measurement is
performed. However, this IC purging step also purges some of the organic molecules, which
can be retrapped, oxidized to CO2, and quantitated as purgeable organic carbon (POC). The
remaining organic matter in the sample is also oxidized to CO2 and quantitated as
nonpurgeable organic carbon (NPOC). In this approach, TOC is the sum of POC and NPOC:
In pharmaceutical waters, the amount of POC is negligible and can be discounted. Therefore,
for the purpose of this methodology, NPOC is equivalent to TOC.
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off-line laboratory test using a calibrated instrument. The suitability of the apparatus must be
periodically demonstrated as described below. In addition, it must have a manufacturer's
specified limit of detection of 0.05 mg of carbon per L (0.05 ppm of carbon) or lower.
Reagent Water—Use water having a TOC level of not more than 0.10 mg per L. [NOTE—A
conductivity requirement may be necessary to ensure method reliability.]
Test Solution—[NOTE—Use extreme caution when obtaining samples for TOC analysis.
Water samples can be easily contaminated during the process of sampling and transportation
to a testing facility.] Collect the Test Solution in a tight container with minimal head space,
and test in a timely manner to minimize the impact of organic contamination from the closure
and container.
Reagent Water Control—Use a suitable quantity of Reagent Water obtained at the same
time as that used in the preparation of the Standard Solution and the System Suitability
Solution.
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following the manufacturer's instructions, and run the appropriate blanks to zero the
instrument.
System Suitability—Test the Reagent Water Control in the apparatus, and record the
response, rw. Repeat the test using the Standard Solution, and record the response, rS.
Calculate the corrected Standard Solution response, which is also the limit response, by
subtracting the Reagent Water Control response from the response of the Standard Solution.
The theoretical limit of 0.50 mg of carbon per L is equal to the corrected Standard Solution
response, rS–rw. Test the System Suitability Solution in the apparatus, and record the
response, rss. Calculate the corrected System Suitability Solution response by subtracting the
Reagent Water Control response from the response of the System Suitability Solution, rss–rw.
Calculate the response efficiency for the System Suitability Solution by the formula:
100[(rss–rw) / (rS–rw)].
The system is suitable if the response efficiency is not less than 85% and not more than
115% of the theoretical response.
Procedure—Perform the test on the Test Solution, and record the response, rU. The Test
Solution meets the requirements if rU is not more than the limit response, rS– rw. This method
also can be performed alternatively using on-line instrumentation that has been appropriately
calibrated, standardized, and has demonstrated acceptable system suitability. The
acceptability of such on-line instrumentation for quality attribute testing is dependent on its
location(s) in the water system. These instrument location(s) and responses must reflect the
quality of the water used.
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